Jump to main content
Jump to site search
Access to RSC content Close the message box

Continue to access RSC content when you are not at your institution. Follow our step-by-step guide.



Intranasal delivery of berberine via in situ thermoresponsive hydrogels with non-invasive therapy exhibits better antidepressant-like effects

Author affiliations

Abstract

The efficacy of antidepressant therapy is frequently limited by challenges related to the potential to reach the brain. The development of new strategies to deliver more antidepressants to the brain so as to bypass the blood–brain barrier (BBB) is beneficial for the treatment of nervous system diseases, especially depression. Here, we have reported an unconventional strategy by the intranasal delivery of berberine with an in situ thermoresponsive hydrogel as the holder in the nasal cavity to improve its antidepressant-like activity. A berberine/hydroxylpropyl-β-cyclodextrin (HP-β-CD) inclusion complex was first prepared to improve the solubility of berberine and loaded into a thermoresponsive hydrogel system of poloxamers. A radioactive tracer of 125I-labeled berberine was used to investigate brain targeting. Liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) was performed to study the pharmacokinetic change in the hippocampus. Monoamine neurotransmitters were analyzed in a reserpine-induced depression model, and metabolomic analysis of the hippocampus was performed in a chronic unpredictable mild stress (CUMS)-induced depression model. The radioactive tracer analysis manifested that the thermoresponsive hydrogel administered intranasally could maintain a high concentration gradient of berberine to the brain, and the relative bioavailability of berberine was enhanced approximately by 110 times that of the oral berberine/HP-β-CD inclusion complex in the hippocampus. The thermoresponsive hydrogel system resulted in similar or better antidepressant-like efficacy even with a lower dosage in reserpine and CUMS-induced depression in rats. The pharmacometabolomics analysis revealed that in addition to increasing the hippocampal monoamine levels, berberine via intranasal administration exhibited a unique mechanism by restoring the mitochondrial dysfunction as well as phospholipid and sphingolipid abnormalities as compared to intragastric (IG) administration. We consider this a safer and more effective strategy with a lower dosage than traditional oral drugs for the treatment of depression.

Graphical abstract: Intranasal delivery of berberine via in situ thermoresponsive hydrogels with non-invasive therapy exhibits better antidepressant-like effects

Back to tab navigation

Supplementary files

Article information


Submitted
15 Dec 2019
Accepted
18 Mar 2020
First published
25 Mar 2020

Biomater. Sci., 2020, Advance Article
Article type
Paper

Intranasal delivery of berberine via in situ thermoresponsive hydrogels with non-invasive therapy exhibits better antidepressant-like effects

Q. Wang, K. Li, L. Gao, Y. Zhang, K. Lin and Y. Cui, Biomater. Sci., 2020, Advance Article , DOI: 10.1039/C9BM02006C

Social activity

Search articles by author

Spotlight

Advertisements